Method and apparatus for treatment of cutaneous and subcutaneous conditions

ABSTRACT

The present invention provides method and apparatus for treating tissue in a region at depth while protecting non-targeted tissue by cyclically applying cooling to the patients skin, and preferably to the region, and by applying radiation to the patient&#39;s skin above the region to selectively heat tissue during and/or after cooling is applied. At least one of cooling and radiation may be applied by successively passing a continuous output applicator over the patient&#39;s skin. Treatment may also be enhanced by applying mechanical, acoustic or electrical stimulation to the region.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/588,746, filed on Jan. 2, 2015 and entitled “Method And Apparatus ForTreatment Of Cutaneous And Subcutaneous Conditions,” which is acontinuation of U.S. patent application Ser. No. 11/865,367, filed onOct. 1, 2007 and entitled “Method And Apparatus For Treatment OfCutaneous And Subcutaneous Conditions,” which is a continuation of U.S.patent application Ser. No. 10/465,757, now U.S. Pat. No. 7,276,058,filed Jun. 19, 2003 and entitled “Method And Apparatus For Treatment OfCutaneous And Subcutaneous Conditions,” which claims priority to U.S.patent application Ser. No. 60/389,871, filed Jun. 19, 2002 and entitled“Method And Apparatus For Subdermal Heating,” all of which areincorporated by reference herein in their entireties.

BACKGROUND

Field of the Invention

This invention relates to methods and apparatus for the photothermaltreatment of tissue and, more particularly, to methods and apparatus fortreating cutaneous and subcutaneous conditions at depth.

Description of the Related Art

The benefits of being able to raise and/or lower the temperature in aselected region of tissue for various therapeutic and cosmetic purposeshas been known for some time. For instance, heated pads or plates orvarious forms of electromagnetic radiation, including visible, infraredand microwave radiation, electricity, and ultrasound have previouslybeen used for heating subdermal muscles, ligaments, bones and the liketo, for example, increase blood flow, to otherwise promote the healingof various injuries and other damage, and for various therapeuticpurposes, such as frostbite or hyperthermia treatment, treatment of poorblood circulation, physical therapy, stimulation of collagen, cellulitetreatment, adrenergic stimulation, wound healing, psoriasis treatment,body reshaping, non-invasive wrinkle removal, etc. The heating oftissues has also been utilized as a potential treatment for removingcancers or other undesired growths, infections and the like. Heating maybe applied over a small localized area, over a larger area, for exampleto the hands or feet, or over larger regions of tissue, including theentire body.

Since most of the techniques described above involve applying energy totissue at depth through the patient's skin surface, peak temperaturegenerally occurs at or near the patient's skin surface and decrease,sometimes significantly, with depth. Further, while microwaves orultrasonic and other acoustic radiation have been used in the past, suchradiation has had limited use because, particularly for microwaves, theymay be potentially mutagenic, may potentially otherwise result in cellor systemic damage and, particularly for acoustic sources, arerelatively expensive. They may also not be practical for large-areatreatment.

While optical and near infrared (NIR) radiation (collectively referredto hereinafter as “optical radiation” is generally both less expensiveand, being non-mutagenic, safer than microwaves radiation, the use ofoptical radiation has heretofore not been considered suitable for mostapplications involving heating of tissue at depth, the term “tissue atdepth” as used herein meaning tissue at the border zone of the dermisand hypodermis or subcutaneous region, some of which tissue may be inthe lower dermis, mostly at a depth deeper than 1 mm, and tissue belowthis border zone to a depth of up to about 50 mm. The reason why thisradiation has not been considered suitable is because such radiation isboth highly scattered and highly absorbed in surface layers of tissue,precluding significant portions of such radiation from reaching thetissue regions at depth to cause heating thereof. In view of the energylosses due to scattering and absorption, substantial optical (includingNIR) energy must be applied in order for enough such energy to reach aregion of tissues at depth to have a desired effect. However, such highenergy can cause damage to the surface layers of tissue andpain/discomfort to the patient, making it difficult to achieve desiredphotothermal treatments in tissue regions at depth. For these reasons,optical radiation has heretofore had at most limited value fortherapeutic and cosmetic treatments on tissue at depth.

While heating or cooling of tissue at depth alone has proved useful formany treatments, the combination of heating and cooling appliedintermittently to the skin surface (known as contrast therapy) is alsoknown and has been suggested for skin improvement, pain relief,inflammation reduction, and healing of injury. Of particular importanceis the application of these techniques for reducing subcutaneous fatdeposits and treating cellulite (gynoid lipodystrophy). However, use ofcooling or heating, either alone or in combination for treatment ofconditions at depth, for example for skin improvement, celluliteimprovement, fat reduction, and treatment of other conditions has beenlimited by the body's pain/discomfort tolerance and by the damage limitsof treated organs and adjacent, especially cutaneous, tissue that needto be kept intact.

A need therefore exists for improved method and apparatus forphotothermal treatment of tissue regions at depth, and in particular fortreatment of deep dermis and subcutaneous regions of tissue, whichtreatments provide improved treatment results, while both reducingpatient pain and discomfort and protecting adjacent and othernon-treatment tissue from damage.

SUMMARY OF THE INVENTION

In accordance with the above, this invention provides a method andapparatus for treating at least a selected target region at depth, asthis term has previously been defined, of a patient's body, whileprotecting non-targeted tissue by utilizing a suitable mechanism to coolthe patient's skin surface to a temperature below normal bodytemperature for a selected duration; utilizing a suitable mechanism toselectively apply radiation to the patient's skin above said regionbefore, during and/or after cooling; and repeating the cooling andradiation application for a selected number of cycles, the temperatureto which the patient's skin is cooled and the duration of cooling beingsufficient to cool the treatment region to a selected temperature belownormal body temperature during at least cooling portions of cycles. Thecooling duration should be at least about 10 seconds, normally beingbetween approximately 10 seconds and 20 minutes. Where radiation isapplied after cooling, the radiation may be applied for approximatelyone second to 4 minutes. The cooling may be performed continuously whilethe radiation is applied at intervals during the cooling. Where theselected region is subcutaneous fat, the selected temperature should below enough to result in at least a selective phase change of at least aportion of the fat. In this case, the radiation should be of sufficientpower and duration and of appropriate wavelength to heat the treatmentregion to at least a temperature where the phase of the fat cells isaltered. Alternatively, the radiation may be of sufficient power andduration and of appropriate wavelength to heat the treatment region to atemperature where at least one of the biophysical and biochemicalcharacteristics of cells in the region is altered. Alternatively, theradiation should be of sufficient power and duration and of appropriatewavelength to heat tissue above the treatment region to protect thetissue, but not to significantly heat the treatment region. For anotherembodiment, the treatment involves cycling cooling and heating of thetreatment region, radiation being applied after cooling and theradiation being of sufficient power and duration and of appropriatewavelength to heat the region to an appropriate temperature to effectthe treatment. For some embodiments, a selected condition of the patientis detected and utilized to control at least a portion of the operation.Stimulation of the selected region may also be utilized before, duringand/or after at least one of the operations, such stimulation beinggenerally at least one of mechanical, acoustic and electrical. Theperiod and/or phase of the treatment cycles may be correlated with asub-circadian rhythm of the patient.

For some embodiments, the radiation is from a continuous wave source andcooling is also performed from a substantially continuously operatingsource. For these embodiments, cooling and radiation application areeach performed by passing an applicator outputting the appropriatesource over the patient's overlying the treatment region at a selectedrate. The same applicator may be used to perform both cooling adradiation application for these embodiments and the applicator myperform both operations during the same pass or separate passes.

In accordance with another aspect of the invention, radiation isselectively delivered to the patients body above the selected region toheat the region; patient tissue above the selected region isconcurrently cooled to a temperature below that of the selected region;and the region is cooled to a temperature below normal body temperaturebefore and/or after the heating of the region.

In accordance with still another aspect of the invention, treatment isperformed by cyclically applying radiation and cooling to the surface ofthe patient's skin above the selected region through at least oneapplicator providing substantially continuous cooling/radiation output,which applicator is passed over the patient's skin over the regionmultiple times for each cooling/radiation cycle.

Other advantages, novel features, and objects of the invention willbecome apparent from the following detailed description of the inventionwhen considered in conjunction with the accompanying drawings, which areschematic and which are not intended to be drawn to scale. In thefigures, each identical, or substantially similar component that isillustrated in various figures is represented by a single numeral ornotation. For purposes of clarity, not every component is labeled inevery figure, nor is every component of each embodiment of the inventionshown where illustration is not necessary to allow those of ordinaryskill in the art to understand the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting embodiments of the present invention will be described byway of example with reference to the accompanying drawings in which:

FIG. 1 is a diagram illustrating the temperature/depth profile of theskin and subcutis at various times after the onset of surface cooling;

FIG. 2 is a diagram illustrating temperature in the human body as afunction of cooling time for various depths;

FIG. 3 is a diagram illustrating the onset time of patient discomfortand of patient pain as a function of skin surface temperature;

FIG. 4 is a schematic diagram of apparatus suitable for practicing theteachings of this invention;

FIG. 5a-5d are diagrams illustrating cooling temperature (T cooling),heating temperature (T heating), temperature in an upper layer of theskin (T upper) and target temperature at depth (T target) relative tonormal core body temperature (T core normal) for successivecooling/heating cycles in a protective mode;

FIGS. 6a-6d are diagrams illustrating cooling temperature (T cooling),heating temperature (T heating), temperature in an upper layer of theskin (T upper) and target temperature at depth (T target) relative tonormal core body temperature (T core normal) for successivecooling/heating cycles in a therapeutic mode;

FIG. 7 is a diagram illustrating the hysterisis of optical transmittancein fat;

FIG. 8a is a cut-away side view of an optical head suitable use inpracticing the teachings of the invention;

FIG. 8b is an enlarged cut-away side view of a portion of the head shownin FIG. 8 a;

FIG. 9 is a diagram illustrating temperature dynamics at different depthin the skin when in multi-scan mode using non-selective heating with theapplicator shown in FIG. 8; and

FIG. 10 is a diagram illustrating temperature dynamics in blood vesselsat different depths in the skin in multi-scan mode using non-selectiveheating with the applicator shown in FIG. 8.

DETAILED DESCRIPTION

Applications in which the invention may be useful include the treatmentof various pathological and cosmetic conditions, particularly skinrejuvenation, wrinkle removal, skin tightening and lifting, reduction ofodor production, hair growth control, acne treatment, cellulite andsubcutaneous fat treatment, physical therapy, muscle and skeletaltreatments, including treatment of spinal cord problems, and treatmentof cumulative trauma disorders (CTD's) such as carpel tunnel syndrome(CTS), tendonitis and bursitis, fibromyalgia, lymphedema and cancertherapy.

The application of thermal energy, either heating or cooling, to tissuemay also be used, for example, in physical therapy treatments, such asto enhance or accelerate wound healing or relieve pain. Beneficialeffects may include a decrease in joint stiffness, an increase in jointextensibility of collagenous structures such as tendons and scar tissue,pain relief, blood-flow changes, or a decrease in muscle spasm andincrease in muscle tone. As another example, large protein molecules mayhave high absorption coefficients, and the heating of protein-richcollagenous tissues may contribute to healing. A wide variety ofconditions may be treated using this invention, for example, but notlimited to, strained tendons, tenosynovitis, torn ligaments, tendonitis,bursitis, torn joint capsules, or torn muscles. Thermal treatment can beeffective on highly metabolic organs such as sebaceous gland, sweatglands and hair follicles. Other processes may be activated ordeactivated within tissue during cooling or heating. Mechanical orelectrical stimulation, such as massage, may also be used in conjunctionwith cooling or heating to achieve benefits greater then can be achievedby either alone. Positive and negative pressure may also be applied tothe skin surface above the treatment region to facilitate the treatment.

In certain embodiments, the present invention may be used fornon-invasive or non-destructive reduction of localized fat deposits. Forexample, the invention may be used to heat fat or adipose cells pasttheir damage temperature, causing cell damage and/or necrosis.Alternatively, the treated cells may undergo apoptosis, resulting incell death. The dead cells may then be removed or resorbed into thebody, for example, by the body's phagocytic or lymphatic systems. Fatreduction may also be achieved by heating fat or adipose cells to anelevated temperature, but below the damage temperature. For example, thefat cells may be heated to a temperature of between about 41° C. andabout 45° C. Under these conditions, applying heat to subcutaneous fatmay activate lipases or metabolize lipids contained within the adiposetissue found within the subcutaneous fat layer, or blood flow mayincrease to the heated area. Additionally, “lipolysis,” or the processof breaking down fat in the body, may be regulated by enzymes sensitiveto temperature, such as HSL (“hormone-sensitive lipase”). Thus,elevating the temperature of the adipose cells may increase thelipolysis rate, and thus contribute to a reduction in subdermal fat inthe area being treated. This temperature can be below the temperaturefor vascular/lymph damage so damaged fatty cells and fatty acids can beeasily removed from the treatment region. Additionally, application ofthe present invention may be used in combination with otherfat-reduction techniques, such as medication, exercise, or adrenergicstimulation.

The invention also includes cooling of the fat tissue to a temperaturebelow normal body temperature, and preferably below the phase transitiontemperature of at least some fraction of the lipid content of fattycells, which temperature is substantially higher then the freezingtemperature of water-containing tissue, preceded or preferably followedby heating the fat to a temperature below its damage threshold.Triglycerides (which constitute the largest fraction of lipids in humanfatty tissue) undergo a series of phase transitions when theirtemperature changes from normal body temperature to either a lower orhigher temperature. Specifically, several crystalline forms can exist.These forms are (in the order of increasing stability): α, β′, and β.The latter crystals are also significantly larger in size (as needle ofa dozen microns length). Crystal formation can be the reason for fattycell dysfunction and shrinkage resulting from mechanical stress on cellstructure and/or destruction of cell metabolism. β crystal formation canthe primer mechanism for fatty cell treatment. When triglycerides arecooled from normal body temperature, formation of α-crystals takesplace. In order to produce more stable forms, β′ first and β second,reverse heating of the crystallized triglycerides is required. Furtherheating leads to complete melting of all crystalline forms.

Therefore, the following process is suggested to initiate formation ofβ-crystals in adipose cells. First, the fatty tissue is cooled to alower-than-normal temperature T_(α) (in the range between 0 and 37 C).This results in α-crystals being formed. Then, the tissue is heated backto a temperature T_(β)>T_(α) but below 37 C, causing formation of β′-and β-crystals. Finally, the tissue can be heated to even highertemperature in order to melt the crystals, and the process can berepeated for a selected number of cycles. The expected final result isdystrophy and decrease in volume of fatty tissue. This process takesplace for all temperature range 0-37 but for lower T_(α) this process ismore effective. Thermal activation of lymph systems in subcutaneous fatcan also be used to treat cellulite by removing proteins from extra cellspaces.

Application of a cooling panel (agent or device) to the skin surfacecauses the temperature of skin and the subcutaneous region or subcutisto drop gradually, as illustrated by FIG. 1. In FIG. 1, curve (1) isafter one minute, curve (2) after five minutes, curve (3) after tenminutes, and curve (4) after thirty minutes of application of a coolingpanel to the skin surface. The depth of the skin/fat ordermis/subcutaneous boundary, shown at 3 mm in FIG. 1, will varydepending on a number of factors including the patient and the portionof the patient's body being treated. The rate of cooling and the finaltemperature depend on the depth of the target and the temperature of theskin surface. FIG. 2 shows the calculated temperature dynamics of thedermis-subcutis junction at 2.5 mm depth and in subcutaneous fat at 7.5mm depth resulting from a constant surface temperature of 0° C.Substantial cooling of targets in the skin can be achieved in the timerange between 10 s and 300 s. Deeper targets in subcutaneous fat needcooling times in the range between 2 min and 30 min. Cooling time can beshortened by simultaneously coupling into the skin pressure or acousticwaves or by intensive massage of cooled skin. The acoustic waves ormechanical massage can increase the heat conductivity of the skin andsubcutaneous fat by forced convection of inter-cellular water.

Depending on the surface temperature and the duration of application, anumber of processes can be initiated in the fatty and other tissues,including, but not limited to:

-   -   Phase transitions in lipids;    -   Changes in regulatory functions of the adipocyte. In particular,        lower temperatures may suppress activity of Alpha2 receptors,        which inhibit adenylate cyclase and cyclic AMP through Gi        protein and thus decrease lypolisis rate. This can lead to        long-term atrophy of fatty cells after cold exposure;    -   Increase of ion concentration in intracellular water. Such an        increase is caused by partial binding of free water in the        course of fat crystallization. Transition of water into bound        state has been demonstrated spectroscopically. As a result,        concentration of ions in the remaining free water increases.        Once the ion concentration exceeds a critical level,        irreversible damage to the vital mechanisms of the cell can        occur;    -   Water crystallization in tissues;    -   Induction of apoptosis;    -   Tissue necrosis;    -   Stimulation of thermogenesis    -   Remodeling of vascular and lymph vessels;    -   Temporal or permanent dysfunction of follicles, sebaceous and        sweat glands.

In practical use, cold exposure time is limited by the onset ofunpleasant and, subsequently, painful sensations. FIG. 3 illustrates thedependence of these onset times on the temperature at the skin surface.As a result, the practical application time may be insufficient toachieve a desired therapeutic effect.

Thermal cycling, comprised of cooling and heating phases, may be used toeliminate both the pain/discomfort and unwanted tissue damage outsidethe target region. It should be emphasized that, although methods anddevices alternating skin surface temperature between hot and cold havepreviously been proposed, the thermal inertia of tissue prevents rapidpropagation of a heat front from the skin surface to a desired treatmentdepth (or vice versa).

This invention therefore uses deep-penetrating electromagnetic oracoustic radiation to create distributed heat sources within tissue.This allows increasing the treatment time substantially and achievingacceptable therapeutic effect, while maintaining both completenon-invasiveness of the procedure and patient comfort.

Beneficial effects of thermal cycling are not limited to treatment offatty tissue. Thermal cycling initiates a number of biophysical andbiochemical responses at molecular, cellular, tissue, and organ levels,including (but not limited to):

-   -   modulation of cell membrane's permeability and, therefore,        inter-membrane transport and exchange between intra- and        interstitial compartments;    -   induction of thermo-mechanical stress in the target (for        example, malignant) cells, leading to cell death through either        necrosis or apoptosis;    -   changes in elasticity and permeability of vessel walls;    -   changes in blood rheology;    -   stimulation of tissue regeneration, including new collagen        generation in skin and subcutis;    -   changes of toxin structure in the interstitial fluid making them        amenable for easy removal by lymphatic systems.

As a result, thermal cycling can be used for treatment of a wide rangeof conditions, involving skin, subcutaneous fat, connective tissues,blood and lymph vasculature, muscles, bones, and other internal organs.

Apparatus for implementing the technical concept is illustrated by FIG.4. This implementation is exemplary, and a suitable configuration can beeasily derived by those skilled in the art for particular applications.The cooling unit can be a thermoelectric element, an enclosure withcooling agent, a stream of cold gas (or liquid) or other cooling unitknown in the art. Phase-changing materials can also be used for cooling.Preferably, skin surface temperature during the cooling phase should bemaintained within the range between 0 C and 25 C. Preferable tissuetemperature on the heating phase is in the range between 25 C and 45 C.In one embodiment of the invention, optical radiation is used on theheating phase of the cycle. In this embodiment, the energy source can bea laser, an LED, a lamp (discharge, halogen or other), or a combinationor an array thereof. The spectral composition of the source can beeither narrow- or broad-band, with the range of wavelengths between 400nm and 2000 nm. Spectral filtration can be used for further modifyingspectral composition of the beam in order to achieve optimalpenetration. The wavelengths used for a particular application willdepend on the target tissue, the depth of the tissue and other factors.The light source is operated preferably in the continuous wave (CW)mode, with a preferred irradiance at the skin surface in the rangebetween 0.1 and 100 W/cm2. The thermal cycle is organized in such a wayas to maximize efficacy of treatment. Typically, duration of the coolingphase can be between 10 sec and 30 min, whereas duration of the heatingphase can be between 1 sec and 4 min. The apparatus of FIG. 4 alsoincludes a power supply for the energy source, a suitable control unit,an optional sensor, the function of which will be discussed later, andother components normally used in such apparatus.

The invention can be practiced in two distinctive modes (See FIGS. 5 and6): in the protective mode, thermal cycling is used to protect adjacent(typically, upper) tissue from unwanted damage; whereas in thetherapeutic mode thermal cycling is used substantially as a treatmentmodality.

The invention can be practiced in at least two distinct modes (See FIGS.5 and 6). In the protective mode of FIG. 5, initially applied coolingrapidly lowers the temperature at the skin surface, the target regionand all tissue therebetween. Before the patient experiences pain ordiscomfort, and before thermal damage occurs outside the target region,a heating phase is initiated. The radiation from the energy source issufficient to raise the temperature at the skin surface and below to adepth above the treatment region to a temperature above a discomfort ordamage temperature, but has little effect on the treatment region atdepth. This results in the temperature of the treatment regioncontinuing to drop slightly with successive cooling cycles. This mode ofthermal cycling is thus used to protect adjacent (typically, upper)tissue from unwanted damage. In the therapeutic mode shown in FIG. 6,thermal cycling is used substantially as a treatment modality. Here, thecooling and radiation parameters are selected so that, during heatingcycles, the temperature at both the surface and the treatment regionrise above normal body temperature, the treatment region thus beingcycled between cold therapy and heat therapy. While in FIG. 6, thetarget region is heated above normal body temperature during heatingportions of each cycle, this is not a limitation on the invention, andcyclically heating the target region to a selected temperature belownormal body temperature may also have therapeutic effect for someconditions. Cycling may also be practiced by heating the target regionto a temperature sufficient to cause hyperthermia, for example 42 to 47°C., either with or without simultaneous cooling to protect overlyingtissue, and then either reducing or removing the radiation or increasingcooling to cool the treatment region below normal body temperature, thisbeing done cyclically.

Thermal cycling offers another advantage when optical radiation is usedas the deep-penetrating energy. Specifically, it has been demonstratedwith optical measurements, that the rate of increase in opticaltransmittance when fresh human fatty tissue is heated exceeds the rateof decrease in optical transmittance when the same tissue is cooled (SeeFIG. 7). There is an indication of accumulated irreversible structuralchange in the fatty tissue caused by thermal cycling in relativelynarrow temperature ranges between 25 and 30 C. As a consequence, thepenetration depth of the optical radiation (and the efficiency of theheating phase) can be augmented by multiple cycling.

In some embodiments, the applicator (handpiece) of the apparatus can berealized as a stationary implement, which is placed on the treatmentarea prior to initiating thermal cycling.

In other embodiments, the handpiece can be manually or mechanicallyscanned along the skin surface (See FIG. 8). Thermal cycling can beperformed concurrently with scanning. Alternatively, thermal cycling canbe implemented by performing at least one (preferably, several) passeson the cooling phase, followed by at least one (preferably, several)passes on the heating phase, and repeating the cycle until desiredtreatment effect is achieved. Referring to FIG. 8a , an exemplaryscanning handpiece is shown which includes a handle 1 and an applicator2. Referring to FIG. 8b , the applicator 2 includes a mount 3, areflector cooling fan 4, an optional pressure or acoustic generator,vibrator or massaging implement 5, a reflector 6, a radiation source (anarc or halogen lamp for the embodiment shown) 7, a cooling plate 8, anoptional wheel 9 functioning as a mechanical velocity sensor, a coolingagent 10 and an optical filter 11.

The apparatus of FIG. 8 can be used, in particular, in a multi-scanmode. The multi-scan mode results in non-uniform cycling of temperatureat different depths. FIG. 9 shows temperature at the epidermis/dermisjunction (0.1 mm depth), dermis/hypodermis junction (2.5 mm depth) andsubcutaneous fat (7.5 mm depth) as a function of time for multi-scanoperation. Calculations have been done for the following conditions:wavelength 800-1800 nm (filtered spectrum of halogen lamp), powerdensity 80 W/cm2, width of optical beam across scanning direction is 1cm, speed of scan is 10 cm/s, length of scan is 50 cm, temperature ofcold sapphire window in contact with the skin is −10° C. For scanningmode, the temperature of the contact plate can be significantly lowerthan the skin freezing temperature and at fast scanning speeds (about 10cm/s), can be as low as −50° C. without risk of cold injury. FIG. 9shows that the amplitude of thermal oscillations decreases with depth inskin. However, the time of stabilization of the temperature for deeptargets can be long: 0.1 mm-100 s or 10 scans, 2.5 mm-5 min or 30 scans,7.5 mm-15 min or 90 scans.

FIG. 10 shows temperatures at the blood vessels in first plexus (0.015mm diameter, 0.1 mm depth), second plexus (0.2 mm diameter, 2.5 mmdepth), and subcutaneous fat (0.1 mm diameter, 7.5 mm depth) as afunction of time for multi-scan operation. Calculations have been donefor the following conditions: wavelength 400-1800 nm (filtered spectrumof halogen lamp), power density 65 W/cm2, width of optical beam acrossscanning direction is 1 cm, speed of scan is 10 cm/s, length of scan is50 cm, temperature of cold sapphire window in contact with the skin is−10° C. FIG. 10 shows that the amplitude of thermal oscillations inblood vessels is significant in the skin and negligible in thesubcutaneous fat. Large temperature oscillations at the vessels in thesecond plexus (up to 10° C.) can be effective for treatment of variousconditions at the deep dermis and dermis/hypodermis junction and forimprovement of cosmetic appearance of cellulite. Since the temperatureof vessels in the subcutaneous fat is continuously rising, thistreatment can be effective for increasing the rate of lypolysis.

Where energy source is a continuous wave (CW) or other long durationsource, the apparatus or device for various of the embodiments may beslid or scanned over the surface of the patient's skin to overliesuccessive treatment regions, the dwell time, and thus the treatmentduration, for each such region being a function of the rate at which thedevice is moved. The device may be moved over each treatment regionmultiple times during a single treatment. Since the device willtypically also include a skin cooling mechanism, concurrent heating andcooling is effected for each region as the device passes thereover. Thedevice may also include a cooling mechanism ahead of the portion of thedevice under the energy source to pre-cool skin above the treatmentregion (see for example issued U.S. Pat. Nos. 6,273,884 and 6,511,475,which are incorporated herein by reference). The power density P_(s) forthis sliding mode of operation is:P _(s) =P ₀ T v/d,

Were P₀ is power density for the organ/region being treated in astationary mode

V is speed of sliding,

d is spot or aperture size in the direction of scanning,

T is interval between two consecutive passes through same spot.

Treatment time isT _(s) =T ₀ T v/d,

where T₀ is the stationary mode treatment time for the organ/regionbeing treated In order for the multiple passes to be beneficial, Tshould be less than the thermal relaxation time of the tissue beingtreated in the region at depth. However, when in either stationary modeor sliding mode, the treatment time can be greater than the thermalrelaxation time of the tissue being treated.

Any of the embodiments can include a contact sensor to assure goodoptical and thermal coupling, and systems operating in the sliding modemay also include one or more motion sensors to control radiationdelivery, cooling and other functions dependent on scanning speed, toenhance system safety and for other reasons.

In addition to coupling the deep heating treatment of this inventionwith deep cooling to enhance treatment of fat, bone, muscle, etc., theapplicator may also include a massager, vibrator or other mechanicalstimulation device, an ultrasonic or other acoustic stimulator or a DCor other suitable electrical stimulation source. It has been found thatsuch mechanical or electrical stimulation is more effective when tissuetemperature deviates from normal body temperature (ie., for hot or coldtissue). Similarly, the effect of deep heating may be enhanced bymassage or other stimulation because both heat and cold generallypenetrates better in compressed skin and subdermal tissue. Thus, thecombination of deep heating and mechanical or electrical stimulation mayprovide significantly better results then either one alone. Heating mayalso be enhanced by supplementing the optical heating with, for exampleelectro-stimulation by AC/DC, or additional heating by RF, etc.Tensioning or pressure applied to the skin overlying the treatmentregion may also enhance treatment effect and decrease patientdiscomfort/pain sensation.

While an optical radiation source has been utilized for preferredembodiments, other forms of electromagnetic radiation such as microwaveor radio frequency radiation can be used on the heating phase of thecycle. Alternatively, acoustic energy can be used. Unless otherwiseindicated, the term radiation, as used herein, shall refer to the outputfrom all such sources. The power of the source utilized should beselected in order to maintain the temperature of the targeted tissuewithin the preferred range.

The effectiveness of the invention may also be further increased bypracticing a thermotolerance regimen. In this mode, the magnitude oftemperature deviations from normal skin surface temperature which apatient can tolerate increases gradually from cycle to cycle, permittingtreatment temperatures, and thus treatment effectiveness to also begradually increased from cycle to cycle. This mode allows furtherincreasing protection of cutaneous tissues from unwanted damage.

It may also be possible to correlate the period and phase of the thermalcycle with sub-circadian biological rhythms of the patient. Suchcombination can further optimize treatment results by using naturallyoccurring oscillations of biochemical activity in cutaneous andsubcutaneous tissues. Furthermore, the temporal structure of the thermalcycling can deviate from simple harmonic oscillations and be comprised,for example, of several, or even an infinite number of harmonics.

In certain embodiments, the cooling implement can be realized as a layer(film, wrap) placed over the treatment region and the irradiatingapplicator can be realized as a head scanned on top of the coolingimplement. Thermal cycling is achieved as a result of multiple passes ofthe irradiating applicator.

Some embodiments of the invention can incorporate a feedback loopbetween the applicator and the control unit. The feedback loop canincorporate a single or multiple sensors registering the state of theapparatus and the treatment area. For example, a thermal sensor can beused to initiate the heating phase of the cycle when tissue temperaturedrops below a certain threshold, and initiate the cooling phase of thecycle when the temperature exceeds another threshold. Other sensor typesinclude, but are not limited to, scanning speed sensors, contactsensors, pressure sensors, skin detectors, and skin response sensors.

In some embodiments of the invention, an additional stimulatingimplement can be integrated into the applicator (see FIG. 8b ). Thepurpose of the implement is to optimize tissue structure and facilitatethermal cycling. The implement can be, for example, mechanical(knitting, rolling, or pulling action) or vacuum (negative/positivepressure in the treatment area). Other forms of tissue stimulation mayalso be utilized, for example, ultrasonic or other acoustic stimulation,or electrical stimulation.

While several embodiments of the invention have been described andillustrated herein, those of ordinary skill in the art will readilyenvision a variety of other means and structures for performing thefunctions and/or obtaining the results and/or advantages describedherein, and each of such variations or modifications is deemed to bewithin the scope of the present invention. More generally, those skilledin the art would readily appreciate that all parameters, dimensions,materials, and configurations described herein are meant to be exemplaryand that actual parameters, dimensions, materials, and configurationswill depend upon specific applications for which the teachings of thepresent invention are used. Those skilled in the art will recognize, orbe able to ascertain using no more than routine experimentation, manyequivalents to the specific embodiments of the invention describedherein. It is, therefore, to be understood that the foregoingembodiments are presented by way of example only and that, within thescope of the appended claims and equivalents thereto, the invention maybe practiced otherwise than as specifically described. The presentinvention is directed to each individual feature, system, materialand/or method described herein. In addition, any combination of two ormore such features, systems, materials and/or methods, if such features,systems, materials and/or methods are not mutually inconsistent, isincluded within the scope of the present invention. In the claims, alltransitional phrases or phrases of inclusion, such as “comprising,”“including,” “carrying,” “having,” “containing,” and the like are to beunderstood to be open-ended, i.e. to mean “including but not limitedto.” Only the transitional phrases or phrases of inclusion “consistingof” and “consisting essentially of” are to be interpreted as closed orsemi-closed phrases, respectively.

What is claimed is:
 1. A method for non-invasively treating subcutaneous fat tissue in a region of a patient's body, comprising: cooling skin surface above a region of a patient's body prior to applying energy thereto; applying energy, using an energy source, to skin surface to reach the region of a patient's body, said applied energy being of sufficient power and duration to raise temperature of said region above normal body temperature; removing the application of energy to said region; and repeating the steps of applying energy to said region and removing the application of energy to said region for a sufficient number of cycles to effect non-invasively any of a cosmetic or a therapeutic treatment in said tissue, thereby increasing treatment time patient can tolerate compared with a treatment time patient can tolerate in absence of repeatedly cycling applying energy to and removing the application of energy to said region; wherein during each of said cycles of applying energy and removing the application of energy the temperature of said region increases when applying energy to reach a peak value and decreases from said peak value when removing the application of energy, and wherein the temperature of said region remains above normal body temperature during said repeated cycles of applying energy and removing the application of the energy.
 2. The method of claim 1, wherein the steps of cooling the skin surface above the region and repeating applying energy to said region and removing the application of energy to said region are performed during a total treatment time of at least 20 minutes.
 3. The method of claim 2 wherein the cooled skin surface temperature is within the range between 0° C. and 25° C.
 4. The method of claim 1 wherein the temperature of said region is raised to a temperature in a range from 42° C. to 47° C.
 5. The method of claim 1 wherein cooling skin surface avoids damaging skin surface.
 6. The method of claim 1 wherein the cosmetic treatment includes cellulite improvement.
 7. The method of claim 1, wherein said tissue is located below skin and at or above subcutis.
 8. The method of claim 1, wherein the cosmetic treatment includes fat reduction.
 9. The method of claim 1, wherein the cosmetic treatment includes skin tightening.
 10. The method of claim 1, wherein the cosmetic treatment includes skin lifting.
 11. A method for non-invasively treating subcutaneous fat tissue in a region of a patient's body, comprising: providing a stationary applicator; cooling skin surface above a region of a patient's body prior to applying energy thereto; applying energy from an energy source to skin surface, using the stationary applicator, to reach a region of a patient's body, said energy being of sufficient power and duration to raise the temperature of said region above normal body temperature; reducing the energy applied from the energy source to said region; and repeating the steps of applying energy to said region, using the stationary applicator, and reducing the energy applied to said region for a sufficient number of cycles to effect non-invasively any of a cosmetic or a therapeutic treatment in said tissue, thereby increasing treatment time patient can tolerate compared with a treatment time patient can tolerate in absence of repeatedly cycling applying energy to and reducing the application of energy to said region; wherein during each of said cycles of applying energy and reducing the energy applied the temperature of said region increases when applying energy to reach a peak value and decreases from said peak value when reducing the energy applied, and wherein the temperature of said region remains above normal body temperature during said repeated cycles of applying energy and reducing the energy.
 12. The method of claim 11 further comprising: cooling the skin surface above the region for a selected duration.
 13. The method of claim 12 wherein the cooled skin surface temperature is within the range between 0° C. and 25° C.
 14. The method of claim 12 wherein cooling is applied prior to applying energy to the skin surface.
 15. The method of claim 11 wherein the temperature of said region is raised to a temperature in a range from 42° C. to 47° C.
 16. The method of claim 11 wherein the cosmetic treatment includes new collagen generation.
 17. The method of claim 11 wherein the cosmetic treatment includes cellulite improvement.
 18. The method of claim 11, wherein said tissue comprises hypodermal tissue.
 19. The method of claim 11, wherein the cosmetic treatment includes fat reduction.
 20. The method of claim 11, wherein the cosmetic treatment includes skin tightening.
 21. The method of claim 11, wherein the cosmetic treatment includes skin lifting.
 22. A method for non-invasively treating subcutaneous fat tissue in a region of a patient's body, comprising: cycling (i) noninvasive application of energy, using an energy source, to a skin surface to reach the tissue region and (ii) removing or reducing the application of energy, wherein cycling the application of energy and removing or reducing the application of energy steps are performed; raising temperature of the tissue region above normal body temperature during cycling; repeating cycling for a sufficient number of cycles to effect fat reduction in the tissue region; maintaining the temperature of the region above normal body temperature during the sufficient number of cycles; and increasing a total treatment time patient can tolerate compared to treatment time patient can tolerate when cycling is not performed, wherein the total treatment time is at least 20 minutes.
 23. The method of claim 22 further comprising cooling the skin surface above the region and increasing a total treatment time patient can tolerate compared to treatment time patient can tolerate when cycling is not performed, at least in part in response to cooling of skin surface to avoid damage thereto. 